BACKGROUNDMutations in the KRAS oncogene occur in approximately 30% of cancer yet little therapeutic options exist for the treatment of these cancers. Various strategies to target KRAS protein or its downstream effectors have not been particularly successful in the past.PURPOSEIn this project we aim to take a different approach to discovery inhibitors of the KRAS oncoprotein. We are using high-throughput chemical screening to identify compounds that specifically causes the degradation of KRAS proteins.SIGNIFICANT MATERIALS AND METHODSAn cell-based assay system that allows one to monitor the effect of small molecules on KRAS protein level in a high-throughput format.FY2012 ACCOMPLISHMENTIn 2011 we have demonstrated the feasibility of the assay in HTS format. In 2012 we have conducted a pilot screen and have identified candidate leads that could serve as positive controls for further screens.